Key Regulator of Bone Cells Linked to Osteoporosis

Osteoclasts are cells that play a major role in the development and remodelling of bone. They originate from the fusion of macrophages and are important mediators of the loss of bone mass that leads to osteoporosis.

Osteoporosis is a serious problem worldwide: it is characterised by loss of bone density leading to fractures in response to relatively mild trauma. Other disorders of localised bone loss include rheumatoid arthritis and periodontal disease.

The research on osteoporosis, led by Associate Professor Agnès Vignery in the Department of Orthopedics and Rehabilitation, focused on interleukin-1 receptor associated kinase M (IRAK-M), an intracellular signalling molecule previously found only in macrophages and in circulating white blood cells.

Their theory was that if IRAK-M is maintained as macrophages fuse to form osteoclasts, it would block later steps in the signal pathway and keep osteoclasts from growing out of control.

"IRAK-M appears to be a key signalling molecule in the prevention of bone loss," said Vignery. "In normal mice the level of IRAK-M in osteoclasts is high compared to what is found in macrophages - and bones are well maintained. Mice that lack IRAK-M develop severe osteoporosis."

The study was done with male mice, and possible association between sex hormones and the expression of IRAK-M remain to be investigated, according to Vignery. "For now, IRAK-M looks like an exciting new target for treating or preventing the devastation of osteoporosis and other localized problems of bone loss,"